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For nearly half a century, a number of conflicting tectonic models have been postulated to explain the enigmatic geological relationship between Tasmania and Victoria, with a view to unifying our understanding of the evolution of the eastern margin of Gondwana in Australia. In this study, ambient noise data from an array of 24 broadband seismometers is used to produce a high-resolution 3-D crustal shear wave velocity model of Bass Strait, the key to understanding the missing link. We apply a novel transdimensional and hierarchical Bayesian inversion approach to construct group velocity maps in the period range of 2–30 s, and subsequently invert group velocity dispersion for 3-D shear wave velocity structure. This allows us to image, for the first time, the entire crust beneath Bass Strait in high detail and elucidate the geometry and position of key crustal features with corroboration from complementary datasets. The three sedimentary basins related to the failed rifting event associated with the Australia–Antarctica breakup, in particular Bass Basin, clearly emerge from the tomographic solution model. A key feature of the 3-D shear wavespeed model is a distinct mid-lower crustal NW–SE high velocity zone which extends from northwestern Tasmania to south-central Victoria, confirming a Proterozoic geological connection. We also image three north–south high velocity belts that appear to span Bass Strait, with some interruption from velocity variations possibly related to more recent tectonic events. These belts are consistent with recent gravity and magnetic maps, and may indicate the presence of an exotic Precambrian terrane (the Selwyn Block). The model also images the crustal velocity structure of the southern Stawell and Bendigo Zones, and their internal large-scale multi-layer characters, a legacy of their Early Paleozoic intra-oceanic origins. Another high velocity anomaly imaged in the mid-lower crust is an east–west lineament beneath the northern part of Bass Strait, which may be an intrusive feature associated with the failed rift. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Adequate reporting is needed to judge methodologic quality and assess the risk of bias of surveys. The objective of this study is to describe the methodology and quality of reporting of surveys published in five critical care journals. DATA SOURCES: All issues (1996-2009) of the American Journal of Respiratory and Critical Care Medicine, Critical Care, Critical Care Medicine, Intensive Care Medicine, and Pediatric Critical Care Medicine. STUDY SELECTION: Two reviewers hand-searched all issues in duplicate. We included publications of self-administered questionnaires of health professionals and excluded surveys that were part of a multi-method study or measured the effect of an intervention. DATA EXTRACTION: Data were abstracted in duplicate. DATA SYNTHESIS: We included 151 surveys. The frequency of survey publication increased at an average rate of 0.38 surveys per 1000 citations per year from 1996-2009 (p for trend = 0.001). The median number of respondents and reported response rates were 217 (interquartile range 90 to 402) and 63.3% (interquartile range 45.0% to 81.0%), respectively. Surveys originated predominantly from North America (United States [40.4%] and Canada [18.5%]). Surveys most frequently examined stated practice (78.8%), attitudes or opinions (60.3%), and less frequently knowledge (9.9%). The frequency of reporting on the survey design and methods were: 1) instrument development: domains (59.1%), item generation (33.1%), item reduction (12.6%); 2) instrument testing: pretesting or pilot testing (36.2%) and assessments of clarity (25.2%) or clinical sensibility (15.7%); and 3) clinimetric properties: qualitative or quantitative description of at least one of face, content, construct validity, intra- or inter-rater reliability, or consistency (28.5%). The reporting of five key elements of survey design and conduct did not significantly change over time. CONCLUSIONS: Surveys, primarily conducted in North America and focused on self-reported practice, are increasingly published in highly cited critical care journals. More uniform and comprehensive reporting will facilitate assessment of methodologic quality. [ABSTRACT FROM AUTHOR]

Abstract Background When planning a randomized controlled trial (RCT), investigators must select randomization and allocation procedures based upon a variety of factors. While third party randomization is cited as being among the most desirable randomization processes, many third party randomization procedures are neither feasible nor cost-effective for small RCTs, including pilot RCTs. In this study we present our experience with a third party randomization and allocation procedure that utilizes current technology to achieve randomization in a rapid, reliable, and cost-effective manner. Methods This method was developed by the investigators for use in a small 48-participant parallel group RCT with four study arms. As a nested study, the reliability of this randomization procedure was prospectively evaluated in this cohort. The primary outcome of this nested study was the proportion of subjects for whom allocation information was obtained by the Research Assistant within 15 min of the initial participant randomization request. A secondary outcome was the average time for communicating participant group assignment back to the Research Assistant. Descriptive information regarding any failed attempts at participant randomization as well as costs attributable to use of this method were also recorded. Statistical analyses included the calculation of simple proportions and descriptive statistics. Results Forty-eight participants were successfully randomized and group allocation instruction was received for 46 (96%) within 15 min of the Research Assistant placing the initial randomization request. Time elapsed in minutes until receipt of participant allocation instruction was Mean (SD) 3.1 +/− 3.6; Median (IQR) 2 (2,3); Range (1–20) for the entire cohort of 48. For the two participants for whom group allocation information was not received by the Research Assistant within the 15-min pass threshold, this information was obtained following a second request at 18 and 20 min, respectively. The method described here produced an email audit trail, which proved useful to the primary study. Conclusions We report a method of third party randomization that uses current technology to operationalize randomization and allocation in a rapid, easy, and cost-effective manner. Other investigators may find this method useful, particularly for small RCTs, including pilot RCTs, on a tight budget.

Objectives: Recent reviews demonstrated discordant effects of ICU-based physical rehabilitation on physical function. These inconsistencies may be related to differences in treatment fidelity-the extent to which a protocol is delivered as planned. Before evaluating the association of fidelity with outcomes, we must first understand the extent of treatment fidelity reporting in ICU-based physical rehabilitation randomized controlled trials (RCTs)., Data Sources: Six electronic databases from inception to December 2022., Study Selection: We included RCTs enrolling adults or children admitted to the ICU, if greater than or equal to 50% were invasively mechanically ventilated greater than 24 hours, and underwent an ICU-based physical rehabilitation intervention, with no limitation to comparators or outcomes., Data Extraction: We screened and extracted data independently and in duplicate, with a third reviewer as needed. Extracted data included study characteristics, treatment descriptions, and the presence of National Institutes of Health Behaviour Change Consortium (NIH-BCC) treatment fidelity tool components. Treatment fidelity scores were calculated as the proportion of reported (numerator) out of total NIH-BCC components (denominator). We calculated scores across studies and by treatment group (intervention vs. comparator). We used linear regression to assess for a time trend in study treatment fidelity scores., Data Synthesis: Of 20,433 citations, 94 studies met inclusion criteria. Authors reported a median (first-third quartiles) of 19% (14-26%) of treatment fidelity components across studies. Intervention group scores were higher than comparator groups (24% [19-33%] vs. 14% [5-24%], p < 0.01). We found a mean increase in study treatment fidelity scores by 0.7% (0.3 points) per year., Conclusions: Only 19% of treatment fidelity components were reported across studies, with comparator groups more poorly reported. Future research could investigate ways to optimize treatment fidelity reporting and determine characteristics associated with treatment fidelity conduct in ICU-based physical rehabilitation RCTs., Competing Interests: Dr. Kho held a Canada Research Chair in Critical Care Rehabilitation and Knowledge Translation from the Canadian Institutes of Health Research during this study. Mr. Farley received support for article research from the Canadian Institutes of Health Research. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Background: We aimed to evaluate the comparative effectiveness and safety of various i.v. pharmacologic agents used for procedural sedation and analgesia (PSA) in the emergency department (ED) and ICU. We performed a systematic review and network meta-analysis to enable direct and indirect comparisons between available medications., Methods: We searched Medline, EMBASE, Cochrane, and PubMed from inception to 2 March 2023 for RCTs comparing two or more procedural sedation and analgesia medications in all patients (adults and children >30 days of age) requiring emergent procedures in the ED or ICU. We focused on the outcomes of sedation recovery time, patient satisfaction, and adverse events (AEs). We performed frequentist random-effects model network meta-analysis and used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach to rate certainty in estimates., Results: We included 82 RCTs (8105 patients, 78 conducted in the ED and four in the ICU) of which 52 studies included adults, 23 included children, and seven included both. Compared with midazolam-opioids, recovery time was shorter with propofol (mean difference 16.3 min, 95% confidence interval [CI] 8.4-24.3 fewer minutes; high certainty), and patient satisfaction was better with ketamine-propofol (mean difference 1.5 points, 95% CI 0.3-2.6 points, high certainty). Regarding AEs, compared with midazolam-opioids, respiratory AEs were less frequent with ketamine (relative risk [RR] 0.55, 95% CI 0.32-0.96; high certainty), gastrointestinal AEs were more common with ketamine-midazolam (RR 3.08, 95% CI 1.15-8.27; high certainty), and neurological AEs were more common with ketamine-propofol (RR 3.68, 95% CI 1.08-12.53; high certainty)., Conclusion: When considering procedural sedation and analgesia in the ED and ICU, compared with midazolam-opioids, sedation recovery time is shorter with propofol, patient satisfaction is better with ketamine-propofol, and respiratory adverse events are less common with ketamine., (Copyright © 2023 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Purpose: We sought to understand the beliefs and practices of Canadian intensivists regarding their use of ketamine as a sedative in critically ill patients and to gauge their interest in a randomized controlled trial (RCT) examining its use in the intensive care unit (ICU)., Methods: We designed and validated an electronic self-administered survey examining the use of ketamine as a sedative infusion for ICU patients. We surveyed 400 physician members of the Canadian Critical Care Society (CCCS) via email between February and April 2022 and sent three reminders at two-week intervals. The survey was redistributed in January 2023 to improve the response rate., Results: We received 87/400 (22%) completed questionnaires. Most respondents reported they rarely use ketamine as a continuous infusion for sedation or analgesia in the ICU (52/87, 58%). Physicians reported the following conditions would make them more likely to use ketamine: asthma exacerbation (73/87, 82%), tolerance to opioids (68/87, 77%), status epilepticus (44/87, 50%), and severe acute respiratory distress syndrome (33/87, 38%). Concern for side-effects that limited respondents' use of ketamine include adverse psychotropic effects (61/87, 69%) and delirium (47/87, 53%). The majority of respondents agreed there is need for an RCT to evaluate ketamine as a sedative infusion in the ICU (62/87, 71%)., Conclusion: This survey of Canadian intensivists illustrates that use of ketamine as a continuous infusion for sedation is limited, and is at least partly driven by concerns of adverse psychotropic effects. Canadian physicians endorse the need for a trial investigating the safety and efficacy of ketamine as a sedative for critically ill patients., (© 2023. Canadian Anesthesiologists' Society.)

Importance: The COVID-19 pandemic created the need for rapid and urgent guidance for clinicians to manage COVID-19 among patients and prevent transmission., Objective: To appraise the quality of clinical practice guidelines (CPGs) using the National Academy of Medicine (NAM) criteria., Evidence Review: A search of MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials to December 14, 2020, and a search of related articles to February 28, 2021, that included CPGs developed by societies or by government or nongovernment organizations that reported pharmacologic treatments of hospitalized patients with COVID-19. Teams of 2 reviewers independently abstracted data and assessed CPG quality using the 15-item National Guideline Clearinghouse Extent of Adherence to Trustworthy Standards (NEATS) instrument., Findings: Thirty-two CPGs were included in the review. Of these, 25 (78.1%) were developed by professional societies and emanated from a single World Health Organization (WHO) region. Overall, the CPGs were of low quality. Only 7 CPGs (21.9%) reported funding sources, and 12 (37.5%) reported conflicts of interest. Only 5 CPGs (15.6%) included a methodologist, described a search strategy or study selection process, or synthesized the evidence. Although 14 CPGs (43.8%) made recommendations or suggestions for or against treatments, they infrequently rated confidence in the quality of the evidence (6 of 32 [18.8%]), described potential benefits and harms (6 of 32 [18.8%]), or graded the strength of the recommendations (5 of 32 [15.6%]). External review, patient or public perspectives, or a process for updating were rare. High-quality CPGs included a methodologist and multidisciplinary collaborations involving investigators from 2 or more WHO regions., Conclusions and Relevance: In this review, few COVID-19 CPGs met NAM standards for trustworthy guidelines. Approaches that prioritize engagement of a methodologist and multidisciplinary collaborators from at least 2 WHO regions may lead to the production of fewer, high-quality CPGs that are poised for updates as new evidence emerges., Trial Registration: PROSPERO Identifier: CRD42021245239.

Objective: To synthesize the available evidence examining the efficacy and safety of levetiracetam compared with phenytoin or fosphenytoin in benzodiazepine-refractory pediatric status epilepticus., Data Sources: We searched (from inception until April 27, 2020) Ovid MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials., Study Selection: Two reviewers, independently and in duplicate, screened citations and manuscripts for eligible randomized controlled trials., Data Extraction and Synthesis: Independently and in duplicate, we performed data abstraction, risk of bias assessment, and certainty assessment using Grading of Recommendations, Assessment, Development, and Evaluation. We performed meta-analyses using random-effect models or, if insufficient data, presented findings narratively., Results: We identified seven randomized controlled trials (n = 1,575). Pooled analysis demonstrated low certainty evidence for no difference of levetiracetam on time to seizure cessation (mean difference, -3.11 min; 95% CI, -6.67 to 0.45), early seizure cessation (relative risk, 1.09, 95% CI, 0.95-1.26), or late seizure cessation (relative risk, 1.05; 95% CI, 0.93-1.18). Adverse event outcomes were limited by low event numbers. We found low certainty evidence for less respiratory depression with levetiracetam (relative risk, 0.28; 95% CI, 0.12-0.69)., Conclusions: The efficacy of levetiracetam is comparable with phenytoin or fosphenytoin in children with benzodiazepine-refractory status epilepticus (low certainty evidence). Levetiracetam may cause less respiratory depression. Clinicians and guideline developers should weigh safety profiles when choosing between these agents., Competing Interests: Dr. Klowak received funding from the Canadian Institutes of Health Research Canada Graduate Scholarship. Dr. Duffett received funding from Hamilton Health Sciences Early Career Research Awards, and he disclosed the off-label product use of Levetiracetam. Dr. Rochwerg received funding from Hamilton Health Sciences Early Career Research Awards. Dr. Jones’ institution received funding from the Hamilton Health Sciences New Investigator Fund Grant, and he received funding from Project ECHO (Epilepsy Across the Lifespan) Ontario Epilepsy. Dr. Choong’s institution received funding from the Academic Health Sciences Alternate Funding Plan Innovation Grant, and she received funding from McMaster University. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Objectives: To examine the gender distribution of authorship of pediatric critical care randomized control trials., Data Sources: The 415 randomized control trials in pediatric critical care published before 2019., Study Selection: We included all randomized control trials enrolling children in a PICU. We used PICUtrials.net, which uses comprehensive search strategies of multiple databases, to identify published randomized control trials., Data Extraction: We manually extracted the name and profession of each listed author from each publication and classified each author as male or female based on their name., Results: We included 2,146 authors and were able to classify 1,888 (88%) as men or women. Overall, 38% of authors were women, this varied with the authorship position: 37% of first, 38% of middle, and 25% of last authors were women (p < 0.001). The three most common professions were physician (63%), nonclinician (11%), and nurse (6%)-of which 30%, 45%, and 97%, respectively, were women. The percentage of female authorship overall has increased from 28% in 1985-1989 to 39% in 2015-2018 (p for trend = 0.004). There were no significant differences in the characteristics of randomized control trials published with a female first or last author versus those with both male first and last authors with respect to the median number of children randomized (60 vs. 50; p = 0.41), multicentred trials (17% vs. 24%; p = 0.12), trials at low risk of bias (50% vs. 66%; p = 0.26), reporting any funding (55% vs. 51%; p = 0.66), or median number of citations per year (1.5 vs. 2.4; p = 0.09)., Conclusions: Although increasing over time, the percentage of researchers publishing pediatric critical care randomized control trials who are women still lags behind the percentage clinicians who are women. Trials that female researchers publish are similar in characteristics and impact as male researchers. Further work should identify barriers to gender diversity and potential solutions in pediatric critical care research.

Background: Optimal drug therapy in children relies on the availability of pediatric-specific information. We aimed to describe the current status of pediatric pharmacotherapy data in monographs of new drugs approved by Health Canada., Methods: In this descriptive analysis, we reviewed the quality and quantity of monographs of new drugs approved by Health Canada between Jan. 1, 2007, and Dec. 31, 2016. We excluded drugs withdrawn from the Canadian market and drugs with primary indications irrelevant to pediatrics. We determined the percentage of included drug monographs that listed pediatric-specific information., Results: During this study period, Health Canada approved 281 drugs, 270 of which met our inclusion criteria. Pediatric-specific information and indication were present in 127 (47.1%) and 75 (27.8%) of the drug monographs, respectively. Of all pediatric age groups, neonates had the lowest number of indications listed in the product monographs (7, 2.6%). Only 9 (60%) oral drugs indicated for children 6 years of age or younger were available in child-friendly, age-appropriate dosage forms., Interpretation: Most of the new drugs approved by Health Canada do not contain pediatric or neonatal indications in their product monographs, and therefore, are used "off-label." Regulatory mechanisms are required to promote both neonatal and pediatric drug development and submission of available pediatric data by manufacturers to Health Canada., Competing Interests: Competing interests: Anthony Chan has a patent issued for antithrombin-heparin covalent complex. No other competing interests were declared., (Copyright 2020, Joule Inc. or its licensors.)

Background: Providing safe and effective sedation to critically ill children is challenging. The assessment, prevention, and treatment of symptoms of iatrogenic withdrawal are critical aspects of sedation practice., Objective: To describe the use of sedative medications in critically ill children at McMaster Children's Hospital., Methods: This retrospective observational study included children admitted over a 12-month period who survived their illness and who received sedation and at least 48 h of invasive ventilation. We collected data from the time of admission to the pediatric intensive care unit to 3 days after discontinuation of sedation., Results: We included 67 children. The median age was 1.6 (interquartile range [IQR] 0.2-6.2) years, and respiratory illnesses were the most common reason for admission (41 [61%]). The children received invasive ventilation for a median of 7 (IQR 4-11) days and sedation for a median of 12 (IQR 6-20) days. Sixty-six children (99%) received an opioid, and all received a benzodiazepine, with median cumulative doses of 14 (IQR 5-27) mg/kg morphine equivalents and 15 (IQR 6-32) mg/kg midazolam equivalents. Dexmedetomidine was given to 31 children (46%), for a median of 8 (IQR 4-12) days. Most children (67%) received sedation after extubation (median duration 7 [IQR 4-14] days). In addition, 32 children (48%) continued to receive sedative medications after transfer to the ward, for a median of 6 (IQR 4-13) days. Forty-two children (63%) had at least one Withdrawal Assessment Tool-1 (WAT-1) score indicative of iatrogenic withdrawal. Children who experienced withdrawal were exposed to more opioids and more benzodiazepines, both per day and overall, and for longer periods., Conclusions: The children in this study were exposed to multiple sedatives, and many continued to receive these medications for an extended period after discontinuation of mechanical ventilation. Iatrogenic withdrawal was common and represents an important opportunity to improve children's recovery after critical illness., Competing Interests: Competing interests: None declared., (2020 Canadian Society of Hospital Pharmacists. All content in the Canadian Journal of Hospital Pharmacy is copyrighted by the Canadian Society of Hospital Pharmacy. In submitting their manuscripts, the authors transfer, assign, and otherwise convey all copyright ownership to CSHP.)

Objective: To describe current stress ulcer prophylaxis practice in Canadian PICUs., Design: Multicenter cohort study. We defined stress ulcer prophylaxis as the use of a proton-pump inhibitor, histamine-2 receptor antagonist, or sucralfate within the first 2 PICU days among children who had not been on these medications at home and had no evidence of gastrointestinal bleeding., Setting: Seven PICUs in Canada., Patients: Three hundred seventy-eight children requiring mechanical ventilation., Interventions: None., Measurements and Main Results: Children were ventilated for a median (interquartile range) of 2 days (1-6 d) and stayed in the PICU for a median (interquartile range) of 4 days (2-10 d). The median (interquartile range) age was 1.3 years (0.3-6.7 yr). Seventy percent of all children received acid suppression during their PICU stay. One hundred sixty-seven (54%) of the 309 children eligible for stress ulcer prophylaxis received it. Histamine-2 receptor antagonists were the most frequently used class (66%), followed by proton-pump inhibitors (47%) and sucralfate (4%), and 20% received more than one class. Stress ulcer prophylaxis was continued on the PICU transfer orders for 34% of these children. Children who received prophylaxis were older and had a higher Pediatric Risk of Mortality III score, more often received nonsteroidal anti-inflammatory drugs and systemic corticosteroids and received less enteral nutrition. In multivariate analysis, age and invasive mechanical ventilation were independently associated with an increased likelihood of receiving stress ulcer prophylaxis and receiving feeds was independently associated with a decreased likelihood of receiving stress ulcer prophylaxis. Gastrointestinal bleeding was reported in 21 (6%) of 378 children; three (0.8%) were clinically important. Eighteen percent were treated for a new respiratory tract infection, and 1% developed Clostridium difficile-associated diarrhea., Conclusions: Stress ulcer prophylaxis is common in Canadian PICUs. Clinically important gastrointestinal bleeding and C. difficile-associated diarrhea are rare, and the utility of routine prophylaxis should be examined.

Objectives: Clinical research is a collaborative enterprise; researchers benefit from the expertise, experience, and resources of their collaborators. We sought to describe the extent and patterns of collaboration among pediatric critical care trialists, and to identify the most influential individuals, centers, and countries., Design: Social network analysis of coauthorship., Data Sources: Publications of pediatric critical care randomized controlled trials (1986-2018)., Data Extraction: We manually extracted the names of all authors and their affiliations. We used productivity (number of randomized controlled trials), influence (number of citations), and four measures of prominence in the social network (degree, betweenness, closeness, and eigenvector centrality) to identify the most influential individuals., Measurements and Main Results: From 415 randomized controlled trials in pediatric critical care, we identified 2,176 trialists from 377 centers in 43 countries. The coauthorship network is highly disconnected and dominated by a single large cluster of trialists publishing 142 (34%) of the randomized controlled trials. However, 119 (29%) of the randomized controlled trials were published by 28 smaller clusters-a median (interquartile range) of 3 (2-4) randomized controlled trials each. The remaining 154 (37%) randomized controlled trials were coauthored by researchers publishing a single randomized controlled trial each. This overall structure has remained constant with the publication of new randomized controlled trials over 33 years. The most influential trialists and centers varied according to the metric we used; only one trialist and three centers ranked in the top 10 for all measures of influence. Thirty-five of the 40 trialists (88%) ranking in the top 10 of any of the measures were from the United States, the United Kingdom, and Canada., Conclusions: Pediatric critical care has made considerable progress in the number of trialists and randomized controlled trials, but the research enterprise remains highly clustered and fragmented, particularly geographically. Efforts to further increase the quantity and quality of research in the field should include steps to increase the level and range of collaboration.

Objectives: Occupational therapists have specialized expertise to enable people to perform meaningful "occupations" that support health, well-being, and participation in life roles. Given the physical, cognitive, and psychologic disability experienced by ICU survivors, occupational therapists could play an important role in their recovery. We conducted a scoping review to determine the state of knowledge of interventions delivered by occupational therapists in adult ICU patients., Data Sources: Eight electronic databases from inception to 05/2018., Study Selection: We included reports of adult patients receiving direct patient care from an occupational therapist in the ICU, all study designs, and quantitative and qualitative traditions., Data Extraction: Independently in duplicate, interprofessional team members screened titles, abstracts, and full texts and extracted report and intervention characteristics. From original research articles, we also extracted study design, number of patients, and primary outcomes. We resolved disagreements by consensus., Data Synthesis: Of 50,700 citations, 221 reports met inclusion criteria, 74 (79%) published after 2010, and 125 (56%) appeared in critical care journals. The three most commonly reported types of interventions were mobility (81%), physical rehabilitation (61%), and activities of daily living (31%). We identified 46 unique original research studies of occupational therapy interventions; the most common study research design was before-after studies (33%)., Conclusions: The role of occupational therapists in ICU rehabilitation is not currently well established. Current interventions in the ICU are dominated by physical rehabilitation with a growing role in communication and delirium prevention and care. Given the diverse needs of ICU patients and the scope of occupational therapy, there could be an opportunities for occupational therapists to expand their role and spearhead original research investigating an enriched breadth of ICU interventions.

Objectives: Characterize current practices for PICU-based rehabilitation, and physician perceptions and attitudes, barriers, resources, and outcome assessment in contemporary PICU settings., Design: International, self-administered, quantitative, cross-sectional survey., Setting: Online survey distributed from March 2017 to April 2017., Patients or Subjects: Pediatric critical care physicians who subscribed to email distribution lists of the Pediatric Acute Lung Injury and Sepsis Investigators, the Pediatric Neurocritical Care Research Group, or the Prevalence of Acute Critical Neurological Disease in Children: A Global Epidemiological Assessment study group, and visitors to the World Federation of Pediatric Intensive and Critical Care Societies website., Interventions: None., Measurements and Main Results: Of the 170 subjects who began the survey, 148 completed it. Of those who completed the optional respondent information, most reported working in an academic medical setting and were located in the United States. The main findings were 1) a large majority of PICU physicians reported working in institutions with no guidelines for PICU-based rehabilitation, but expressed interest in developing and implementing such guidelines; 2) despite this lack of guidelines, an overwhelming majority of respondents reported that their current practices would involve consultation of multiple rehabilitation services for each case example provided; 3) PICU physicians believed that additional research evidence is needed to determine efficacy and optimal implementation of PICU-based rehabilitation; 4) PICU physicians reported significant barriers to implementation of PICU-based rehabilitation across centers; and 5) low routine assessment of long-term functional outcomes of PICU patients, although some centers have developed multidisciplinary follow-up programs., Conclusions: Physicians lack PICU-based rehabilitation guidelines despite great interest and current practices involving a high degree of PICU-based rehabilitation consultation. Data are needed to identify best practices and necessary resources in the delivery of ICU-based multidisciplinary rehabilitation and long-term functional outcomes assessment to optimize recovery of children and families affected by critical illness.

Objectives: Clinical research is a complex scientific and social enterprise. Our objective was to identify strategies that pediatric critical care trialists consider acceptable, feasible, and effective to improve the design and conduct randomized controlled trials in pediatric critical care., Design: Qualitative descriptive study using semistructured individual interviews., Subjects: We interviewed 26 pediatric critical care researchers from seven countries who have published a randomized controlled trial (2005-2015). We used purposive sampling to achieve diversity regarding researcher characteristics and randomized controlled trial characteristics., Interventions: None., Measurements and Main Results: Most participants (24 [92%]) were from high-income countries, eight (31%) had published more than one randomized controlled trial, 17 (65%) had published a multicenter randomized controlled trial, and eight (31%) had published a multinational randomized controlled trial. An important theme was "building communities"-groups of individuals with similar interests, shared experiences, and common values, bound by professional and personal relationships. Participants described a sense of community as a source of motivation and encouragement and as a means to larger, more rigorous trials, increasing researcher and clinician engagement and maintaining enthusiasm. Strategies to build communities stressed in-person interactions (both professional and social), capable leadership, and trust. Another important theme was "getting started." Participants highlighted the importance of formal research training and high-quality experiential learning through collaboration on other's projects, guided by effective mentorship. Also important was "working within the system"-ensuring academic credit for a range of contributions, not only for the principal investigator role. The longitudinal notion of "building on success" was also underscored as a cross-cutting theme., Conclusions: Coordinated, deliberate actions to build community and ensure key training and practical experiences for new investigators may strengthen the research enterprise in pediatric critical care. These strategies, potentially in combination with other novel approaches, may vitalize clinical research in this field.

Objectives: To identify, in addition to survival, preferred outcome measures of PICU family care providers and PICU healthcare professionals for interventional trials enrolling critically ill children, and to describe general attitudes of family care providers and healthcare professionals regarding research in the PICU., Design: Cross-sectional survey examining subject experience with clinical research and personal preferences for outcome measures for a hypothetical interventional clinical trial., Setting: PICUs within four academic children's hospitals in the United States and Canada., Subjects: Two cohorts including family members of critically ill children in PICUs (family care providers) and multidisciplinary staff working in the PICUs (healthcare professionals)., Interventions: Administration of a short, deidentified survey., Measurements: Demographic data were collated for the two subject groups. Participants were queried regarding their attitudes related to research conducted in the PICU. In addition to survival, each group was asked to identify their three most important outcomes for an investigation examining whether or not an intervention helps seriously ill children recover., Main Results: Demographics for family care providers (n = 40) and healthcare professionals (n = 53) were similarly distributed. Female respondents (79.8%) predominated. Participants (98.9%) ascertained the importance of conducting research in the PICU, but significant challenges associated with this goal in the high stress PICU environment. Both quality of life and functioning after leaving the hospital were chosen as the most preferred outcome measure, with 77.5% of family care providers and 84.9% of healthcare professionals indicating this choice. Duration of organ dysfunction was identified by 70.0% of family care providers and 40.7% of healthcare professionals as the second most preferred outcome measure., Conclusions: In addition to survival, long-term quality of life/functional status and duration of organ dysfunction represent important interventional trial outcome measures for both families of critically ill children, as well as the multidisciplinary team who provides critical care.

Background: Stress ulcer prophylaxis is commonly used in pediatric critical care, to prevent upper gastrointestinal bleeding. The most frequently used agents are histamine-2 receptor antagonists (H2RAs) and proton pump inhibitors (PPIs). The risk-benefit ratio for stress ulcer prophylaxis is uncertain, because data from randomized clinical trials (RCTs) on the effectiveness and harms of prophylaxis in children are limited., Objective: To describe the views of Canadian pediatric intensivists about a future RCT of stress ulcer prophylaxis., Methods: We conducted an online survey of Canadian pediatric critical care physicians. We e-mailed information about the study and a link to a 10-item survey to 111 potential respondents, with 2 reminders for nonrespondents. We assessed the relationship between respondents' characteristics and their views about the need for and potential participation in a trial using logistic regression and assessed regional differences using the χ 2 test., Results: The 68 physicians who replied (61% of potential respondents) had a median of 12 (interquartile range 5-20) years of experience. Forty-four (65%) of the respondents stated that a large, rigorous RCT of stress ulcer prophylaxis in children is needed, and 94% (62 of 66) indicated that it should include a placebo group. The 3 most common designs suggested were a 3-arm trial comparing PPI, H2RA, and placebo (56% [37 of 66 respondents to this question]) and 2-arm trials comparing PPI with placebo (15% [ n = 10]) and H2RA with placebo (8% [ n = 5]). The 5 patient groups that respondents most commonly stated should be excluded (because they should not receive placebo) were children receiving acid suppression at home (66% [42 of 64 respondents to this question]) or corticosteroids (59% [ n = 38]), those with severe coagulopathy or receiving extracorporeal membrane oxygenation (both 36% [ n = 23]), and those with burns (31% [ n = 20]). Most respondents indicated a willingness to participate in an RCT (64% [42 of 66 respondents to this question]), whereas some (29% [ n = 19]) indicated that participation would depend on trial design or funding; only 8% ( n = 5) were disinclined to participate., Conclusions: There is considerable interest in a placebo-controlled RCT of stress ulcer prophylaxis among pediatric critical care physicians in Canada, but consensus on key elements of the trial design is needed., Competing Interests: Competing interests: None declared.

Background: Despite sparse pediatric data on effectiveness, the majority of critically ill children receive medications to prevent gastrointestinal (GI) bleeding. Stress ulcer prophylaxis may have unintended consequences-increasing the risk of nosocomial infections-which may be more serious and common than the bleeding which these drugs are prescribed to prevent. Randomized controlled trials (RCTs) in pediatric critical care are exceptionally challenging to complete, thus a rigorous pilot RCT is crucial. The objective of this pilot RCT is to assess the feasibility of a large multicentre RCT of stress ulcer prophylaxis with pantoprazole to prevent upper GI bleeding vs. placebo., Methods: A multi-centre blinded pilot RCT of 120 children in six Canadian PICUs. Children expected to require mechanical ventilation for more than 48 h will be randomized to receive intravenous pantoprazole 1 mg/kg or identical placebo once daily until they no longer need mechanical ventilation. We have four feasibility outcomes and will consider the trial successful if we achieve:Effective screening: If >80% of eligible patients are approached for consent.Timely enrollment: if >80% of participants receive their first dose of the assigned study drug within 1 day of becoming eligible.Participant accrual: If the average monthly enrolment is two or more participants per centre per month.Protocol adherence: if >90% of doses are administered according to the protocol., Discussion: There are many uncertainties about the risks and benefits of stress ulcer prophylaxis. In an era of widespread use-where clinicians prescribe prophylaxis to the more severely ill-a large, rigorous RCT is required. A trial to determine if a strategy of withholding stress ulcer prophylaxis is not inferior to a strategy of routine stress ulcer prophylaxis will be challenging. A carefully designed and implemented pilot trial is essential., Trial Registration: ClinicalTrials.gov:NCT02929563 (Registered October 3, 2016).

Objectives: High-quality, adequately powered, randomized controlled trials are needed to inform the care of critically ill children. Unfortunately, such evidence is not always available. Our objective was to identify barriers and facilitators of conducting high-quality randomized controlled trials in pediatric critical care, from the perspective of trialists in this field., Design: Self-administered online survey. Respondents rated the importance of barriers and effectiveness of facilitators on seven-point scales., Setting: Authors of 294 pediatric critical care randomized controlled trials (published 1986 to June 2015)., Subjects: One hundred sixteen researchers from 25 countries participated., Interventions: None., Measurements and Main Results: Respondents reported a median (Q1, Q3) of 21 years (15, 26 yr) of experience and 41 (36%) had authored more than one randomized controlled trial. More survey respondents, compared with nonrespondents, had published more than one trial (35% vs 26%; p = 0.002) and their trials were more often cited (median citations/yr, 2.4 vs 1.5; p < 0.001). Of the barriers listed, the five most important were primarily related to lack of funding. The five facilitators perceived as most effective were protected time for research, ability to recruit participants 24 hours per day/7 days per week, conducting randomized controlled trials in collaboration with a research network, funding from government agencies specifically for randomized controlled trials in critically ill children, and academic department support for conducting randomized controlled trials. Respondent experience and country income level were associated with differences in importance ratings for eight of 41 barriers. There were fewer such differences for facilitators., Conclusions: Lack of funding and time are major barriers to conducting pediatric critical care randomized controlled trials worldwide. Although barriers varied among country income levels, the facilitators of such trials were more consistent. In addition to increased funding, respondents identified other strategies such as research networks that are within the purview of the pediatric critical care research community, to facilitate the conduct of rigorous randomized controlled trials.

Objective: To evaluate all published pediatric randomized controlled trials of patients with septic shock from any cause to examine the outcome measures used, the strengths and limitations of these measurements and whether the trial outcomes met feasibility criteria., Data Sources: We used a previously published database of pediatric critical care randomized controlled trials (PICUtrials.net) derived from searches of MEDLINE, EMBASE, LILACS, and CENTRAL., Study Selection: We included randomized controlled trials of interventions to children admitted to a PICU with septic or dengue hemorrhagic shock which were published in English., Data Extraction: Study characteristics and outcomes were retrieved by two independent reviewers with disagreement being resolved by a third reviewer. We defined feasibility as 1) recruitment of at least 90% of the targeted sample size and agreement of the observed outcome rate in the control group with the rate used for the sample size calculation to within 10% or 2) finding of a statistically significant difference in an interim or final analysis., Data Synthesis: Nineteen of 321 identified articles were selected for review. Fourteen of 19 studies (74%) provided an a priori definition of their primary outcome measure in their "Methods section." Mortality rate was the most commonly reported primary outcome (8/14; 57%), followed by duration of shock (4/14; 29%) followed by organ failure (1/14; 7%). Only three of 19 included trials met feasibility criteria., Conclusions: Our review found that use of mortality alone as a primary outcome in pediatric septic shock trials was associated with significant limitations and that long-term patient-centered outcomes were not used in this setting. Composite outcomes incorporating mortality and long-term outcomes should be explored for use in future pediatric septic shock trials.

Background: This systematic review and meta-analysis investigates the efficacy and safety of clonidine as a sedative in critically ill patients requiring invasive mechanical ventilation., Methods: We performed a comprehensive search of MEDLINE, EMBASE, CINAHL and the Cochrane trial registry. We identified RCTs that compared clonidine to any non-clonidine regimen in critically ill patients, excluding neonates, requiring mechanical ventilation. The GRADE method was used to assess certainty of evidence., Results: We included eight RCTs (n = 642 patients). In seven of the trials clonidine was used for adjunctive rather than stand-alone sedation. There was no difference in the duration of mechanical ventilation (mean difference (MD) 0.05 days, 95% confidence interval (CI) = -0.65 to 0.75, I 2  = 86%, moderate certainty), ICU mortality (relative risk (RR) 0.98, 95% CI = 0.51 to 1.90, I 2  = 0%, low certainty), or ICU length of stay (MD 0.04 days, 95% CI = -0.46 to 0.53, I 2  = 16%, moderate certainty), with clonidine. There was a significant reduction in the total dose of narcotics (standard mean difference (SMD) -0.26, 95% CI = -0.50 to -0.02, I 2  = 0%, moderate certainty) with clonidine use. Clonidine was associated with increased incidence of clinically significant hypotension (RR 3.11, 95% CI = 1.64 to 5.87, I 2  = 0%, moderate certainty)., Conclusions: Until further RCTs are performed, data remains insufficient to support the routine use of clonidine as a sedative in the mechanically ventilated population. Clonidine may act as a narcotic-sparing agent, albeit with an increased risk of clinically significant hypotension.

Background: Delirium is a syndrome characterized by acute fluctuations and alterations in attention and arousal. Critically ill patients are at particularly high risk, and those that develop delirium are more likely to experience poor clinical outcomes such as prolonged duration of ICU and hospital length of stay, and increased mortality. Melatonin and melatonin agonists (MMA) have the potential to decrease the incidence and severity of delirium through their hypnotic and sedative-sparing effects, thus improving health-related outcomes. The objective of this review is to synthesize the available evidence pertaining to the efficacy and safety of MMA for the prevention and treatment of ICU delirium., Methods: We will search Ovid MEDLINE, Web of Science, EMBASE, PsycINFO, the Cochrane Central Register of Controlled Trials (CENTRAL), and CINAHL to identify studies evaluating MMA in critically ill populations. We will also search http://apps.who.int/trialsearch for ongoing and unpublished studies and PROSPERO for registered reviews. We will not impose restrictions on language, date, or journal of publication. Authors will independently screen for eligible studies using pre-defined criteria; data extraction from eligible studies will be performed in duplicate. The Cochrane Risk of Bias Scale and the Newcastle-Ottawa Scale will be used to assess the risk of bias and quality of randomized and non-randomized studies, respectively. Our primary outcome of interest is delirium incidence, and secondary outcomes include duration of delirium, number of delirium- and coma-free days, use of physical and chemical (e.g., antipsychotics or benzodiazepines) restraints, duration of mechanical ventilation, ICU and hospital length of stay, mortality, long-term neurocognitive outcomes, hospital discharge disposition, and adverse events. We will use Review Manager (RevMan) to pool effect estimates from included studies. We will present results as relative risks with 95% confidence intervals for dichotomous outcomes and as mean differences, or standardized mean differences, for continuous outcomes., Discussion: Current guidelines make no pharmacological recommendations for either the prevention or treatment of ICU delirium. This systematic review will synthesize the available evidence on the efficacy and safety of MMA for this purpose, thus potentially informing clinical decision-making and improving patient outcomes., Systematic Review Registration: PROSPERO CRD42015024713.

Objectives: Research networks in adult and neonatal critical care have demonstrated collaborative and successful execution of clinical trials. Such networks appear to have been relatively recently established in the field of pediatric critical care. The objective of this study was to evaluate the productivity and impact of randomized controlled trials conducted by pediatric critical care research networks, compared with nonnetwork trials., Data Sources, Study Selection, and Data Abstraction: We searched multiple online databases including MEDLINE, reference lists of randomized controlled trials, and relevant systematic reviews. Independent pairs of reviewers identified published randomized controlled trials administering any intervention to children in a PICU and abstracted data. A research network was defined as a formal consortium or collaborative research group established for the purpose of conducting clinical research. Data were independently abstracted in duplicate., Main Results: There were 288 pediatric critical care randomized controlled trials published in English between 1986 and July 2015, of which 15 randomized controlled trials (5.2%) were conducted by a total of five research networks. Network randomized controlled trials were more often multicentered, multinational, and larger in size (p < 0.001), compared with nonnetwork randomized controlled trials. Accordingly, their trials took longer to complete (median, 36 vs 21 mo; p < 0.001). Early stopping occurred in 46.7% of network randomized controlled trials (46.7%) and 27% of nonnetwork randomized controlled trials (p = 0.14), most commonly for futility. None of the network, but 45% of the nonnetwork trials found a significant difference in their primary outcome (p < 0.001). Network trials were more frequently cited (median, 6 vs 2 citations per year) and published in higher impact journals (median impact factor, 21.8 vs 3; p < 0.001)., Conclusions: Research networks have conducted a minority of randomized controlled trials in pediatric critical care. They infrequently demonstrate significant differences in their primary outcomes. Despite this, network trials are cited more frequently and appear to have greater impact. There are important lessons to learn from both individual researchers as well as research networks that may guide the successful conduct of collaborative, high-quality randomized controlled trials in critically ill children.

Purpose: Stress ulcer prophylaxis (SUP) using histamine-2-receptor antagonists has been a standard of care in intensive care units (ICUs) for four decades. Proton pump inhibitors (PPIs) are increasingly used despite apparently lower background rates of gastrointestinal bleeding and growing concerns about PPI-associated complications. Our objective was to understand the views and prescribing habits amongst Canadian physicians regarding SUP in the ICU and to gauge interest in a future randomized-controlled trial (RCT)., Methods: We created a short self-administered survey about SUP for critically ill adults, evaluated its clinical sensibility, and pilot tested the instrument. We surveyed all physician members of the Canadian Critical Care Trials Group (CCCTG) by e-mail and sent reminders three and five weeks later., Results: We received 94 of 111 (85%) surveys from the validated respondent pool between May and June, 2015. Respondents reported use of SUP most commonly in patients 1) receiving invasive mechanical ventilation (62, 66%), 2) expected to be ventilated for ≥ two days (25, 27%), or 3) receiving mechanical ventilation but nil per os (NPO) (20, 21%). Stress ulcer prophylaxis is discontinued when patients no longer receive mechanical ventilation (75%), no longer are NPO (22%), or are discharged from the ICU (19%). Stress ulcer prophylaxis involves PPIs in 68% of centres. Most respondents endorsed the need for a large rigorous RCT of PPI vs placebo to understand the risks and benefits of this practice., Conclusions: Stress ulcer prophylaxis is reportedly used primarily for the duration of mechanical ventilation. The CCCTG physicians believe that a placebo-controlled RCT is needed to evaluate the effectiveness and safety of contemporary SUP with PPIs.

Background: Seamless and safe discharge of children from hospital requires successful collaboration with community pharmacists, for whom pediatrics is often a small part of their practice., Objectives: The purpose of this study was to understand community pharmacists' comfort level and confidence in providing care for children., Methods: We conducted a self-administered online survey of community pharmacists in Ontario, Canada. Respondents rated their comfort and confidence on a scale of 1 to 7 in each of 3 scenarios: oral morphine, prednisone, and amoxicillin. We also evaluated the relationship between participants' comfort level and demographics., Results: We included 622 responses (377 completed and 245 partially completed surveys). A total of 182 participants (48%) were female, 271 participants (72%) had children of their own, and they had practiced pharmacy for a median (interquartile range) of 19 (5-28) years. The percentage of respondents who were comfortable (5-7 on a 7-point scale) with filling the prescriptions as written was 64% for morphine, 58% for prednisone, and 61% for amoxicillin and was not different among the scenarios. Having children was associated with increased comfort (p = 0.02), whereas other demographic variables were not. Compared to the amoxicillin scenario, pharmacists reported being significantly more likely to choose another course of action for prednisone (p = 0.01) but not for morphine (p = 0.25). Although 428 pharmacists (70%) agreed that they maintained adequate knowledge of pediatric topics, 558 (91%) were interested in more education., Conclusions: Variability exists in the confidence and comfort levels of community pharmacists when dealing with children, and many are not comfortable with the common prescriptions in this survey.

Purpose: The primary objective of this survey was to describe pharmacists' attitudes regarding probiotic use in the intensive care unit (ICU); secondary objectives were to evaluate pharmacists' knowledge and use of probiotics for critically ill patients., Methods: The survey instrument was rigorously designed and pretested, then distributed in both English and French to Canadian ICU pharmacists. The online survey was open for 5 weeks, and 3 follow-up emails were sent to maximize response rates., Results: Of 303 eligible surveys, 191 were returned (63.0%). Probiotics were available in the hospitals of 69.8% (113/162) of respondents, and 62.0% (101/163) indicated that they had used probiotics for at least 1 ICU patient in the previous year. Most pharmacists (137/171, 80.1%) said that they would "never" consider recommending probiotics for prevention of ventilator-associated pneumonia in ICU patients, and this response was more common (P = .0074) among pharmacists who were "unsure" about the safety of probiotics in this population when compared to those who felt that they knew how safe probiotics are., Conclusions: Most Canadian ICU pharmacists have used probiotics at least once in the ICU in the last year. However, based on uncertain efficacy and safety, most ICU pharmacists would not currently recommend probiotics for the prevention of ventilator-associated pneumonia., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Abrupt discontinuation of benzodiazepines often results in side effects including anxiety and insomnia, which can be barriers to discontinuation among long-term users. Melatonin improves the onset, duration, and quality of sleep. By preventing insomnia in those attempting to discontinue benzodiazepines, melatonin may facilitate benzodiazepine discontinuation., Objectives: The primary objective was to determine the effect of melatonin compared with placebo on benzodiazepine discontinuation in adults attempting to discontinue benzodiazepines. The secondary objective was to determine the effect of melatonin on sleep quality in this population., Methods: We searched PubMed, MEDLINE, EMBASE, PsychINFO, and ClinicalTrials.gov from inception to November 2014. We included randomized controlled trials published in English comparing melatonin with placebo that reported benzodiazepine discontinuation or sleep quality. Two reviewers independently screened trials, extracted data, and assessed the risk of bias., Results: We included six trials randomizing 322 participants. The mean age of participants was approximately 64 years. The trials used varied tapering strategies to discontinue benzodiazepines over 4-10 weeks while using melatonin. Melatonin had no effect on the odds of successfully discontinuing benzodiazepines (odds ratio 0.72, 95% confidence interval 0.21-2.41, p = 0.59). There was important heterogeneity among the trials (I (2) = 76%). The effect of melatonin on sleep quality was inconsistent., Conclusions: Melatonin had no effect on benzodiazepine discontinuation while the effect of melatonin on sleep quality was inconsistent. We cannot rule out a role of melatonin in improving benzodiazepine discontinuation or sleep quality owing to imprecise effect estimates. Larger, well-designed, and reported randomized controlled trials may provide more valid and precise estimates of the effect of melatonin on these outcomes.

Background: Management and choice of sedation is important during critical illness in order to reduce patient suffering and to facilitate the delivery of care. Unfortunately, medications traditionally used for sedation in the intensive care unit (ICU) such as benzodiazepines and propofol are associated with significant unwanted effects. Clonidine is an alpha-2 selective adrenergic agonist that may have a role in optimizing current sedation practices in the pediatric and adult critically ill populations by potentially minimizing exposure to other sedative agents., Methods/design: We will search MEDLINE, EMBASE, CINAHL, ACPJC, the Cochrane trial registry, World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), and clinicaltrials.gov for eligible observational studies and randomized controlled trials investigating the use of clonidine as an adjunctive or stand-alone sedative agent in patients requiring invasive mechanical ventilation. Our primary outcome is the duration of mechanical ventilation. Secondary outcomes include the following, listed by priority: duration of sedation infusions, dose of sedation used, level of sedation, incidence of withdrawal from other sedatives, delirium incidence, ICU and hospital length of stay, use and duration of non-invasive ventilation, and all-cause ICU and hospital mortality. We will also capture unwanted effects potentially associated with clonidine administration such as clinically significant hypotension or bradycardia, clonidine withdrawal, self-extubation, and the accidental removal of central intravenous lines and arterial lines. We will not apply any publication date, language, or journal restrictions. Two reviewers will independently screen and identify eligible studies using predefined eligibility criteria and then review full reports of all potentially relevant citations. A third reviewer will resolve disagreements if consensus cannot be achieved. We will use Review Manager (RevMan) to pool effect estimates from included studies across outcomes. We will present the results as relative risk (RR) with 95 % confidence intervals (CI) for dichotomous outcomes and as mean difference (MD) or standardized mean difference (SMD) for continuous outcomes with 95 % CI. We will assess the quality of evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach., Discussion: The aim of this systematic review is to summarize the evidence on the efficacy and safety of clonidine as a sedative agent in the critically ill population., Systematic Review Registration: PROSPERO CRD42015019365.

Objectives: Pilot trials are smaller randomized controlled trials conducted to inform the design and assess the feasibility of a large-scale trials. The objectives of this systematic review were to describe pilot trials in pediatric critical care, their conclusions about the clinical implications of the results, and the need for future research and to determine the frequency of large follow-up trials., Data Sources: The Evidence in Pediatric Intensive Care database (http://epicc.mcmaster.ca), a comprehensive repository of published pediatric critical care randomized controlled trials and the World Health Organization's Clinical Trials Registry Platform., Study Selection: Randomized controlled trials described in the publication as "pilot," "feasibility," "proof-of-concept," "exploratory," "phase 2," "vanguard," or "preliminary.", Data Extraction: Pairs of reviewers screened studies for eligibility and abstracted data independently., Data Synthesis: We found 32 pilot trials (12.2% of all pediatric critical care randomized controlled trials) published before July 2014, varying in size from 6 to 165 children. Pilot trials were significantly smaller than those not described as pilots, but other key characteristics were not significantly different. The authors of 16 publications (48.4%) included explicit and specific conclusions about the design or feasibility of larger trials based on the results of the pilot trial. In 20 publications (64.5%), the authors made conclusions about clinical efficacy based on results of the pilot trial. Four of the 32 pilot trials (12.9%) led to larger trials, two of which have been published., Conclusions: Published pilot trials in pediatric critical care often focus on clinical outcomes. They uncommonly report explicit feasibility outcomes, criteria for success, or rationale for the pilot sample size. These pilot trials infrequently lead to larger trials. Understanding and addressing the reasons for this are key to the success of pediatric critical care research.

Objective: Changing clinician practice in pediatric critical care is often difficult. Tailored knowledge translation interventions may be more effective than other types of interventions. To inform the design of tailored interventions, the primary objective of this survey was to describe the importance of specific factors that influence physicians and pharmacists when they make decisions about medications in critically ill children., Design: In this postal survey, respondents used 7-point scales to rate the importance of specific factors that influence their decisions in the following scenarios: corticosteroids for shock, intensive insulin therapy, stress ulcer prophylaxis, surfactant for acute respiratory distress syndrome, and sedation interruption. We used generalized estimating equations to examine the association between the importance of specific factors influencing decision making and the scenario and respondents' practice, views, and demographics., Setting: Canadian PICUs., Participants: One hundred and seventeen physicians and pharmacists practicing in 18 PICUs., Interventions: None., Measurements and Main Results: The response rate was 61%. The three factors reported to most strongly influence clinician decision making overall were: severity of illness (mean [SD] 5.8 [1.8]), physiologic rationale (5.2 [1.3]), and adverse effects (5.1 [1.9]). Factors least likely to influence decision making were drug costs (2.0 [1.5]), unit policies (2.9 [1.9]), and non-critical care randomized controlled trials (3.1 [1.9]). The relative importance of 8 of the 10 factors varied significantly among the five scenarios: only randomized controlled trials in critically ill children and other clinical research did not vary. Clinician characteristics associated with the greatest difference in importance ratings were: frequent use of the intervention in that scenario (seven factors), profession (five factors), and respondents' assessment of the quality of evidence (five factors)., Conclusions: The relative importance of many factors that clinicians consider when making decisions about medications varies by demographics, and depends on the clinical problem. This variability should be considered in quality improvement and knowledge translation interventions in this setting.

Background and Objectives: Survey research is an important research method used to determine individuals' attitudes, knowledge, and behaviors; however, as with other research methods, inadequate reporting threatens the validity of results. This study aimed to describe the quality of reporting of surveys published between 2001 and 2011 in the field of nephrology., Design, Setting, Participants, & Measurements: The top nephrology journals were systematically reviewed (2001-2011: American Journal of Kidney Diseases, Nephrology Dialysis Transplantation, and Kidney International; 2006-2011: Clinical Journal of the American Society of Nephrology) for studies whose primary objective was to collect and report survey results. Included were nephrology journals with a heavy focus on clinical research and high impact factors. All titles and abstracts were screened in duplicate. Surveys were excluded if they were part of a multimethod study, evaluated only psychometric characteristics, or used semi-structured interviews. Information was collected on survey and respondent characteristics, questionnaire development (e.g., pilot testing), psychometric characteristics (e.g., validity and reliability), survey methods used to optimize response rate (e.g., system of multiple contacts), and response rate., Results: After a screening of 19,970 citations, 216 full-text articles were reviewed and 102 surveys were included. Approximately 85% of studies reported a response rate. Almost half of studies (46%) discussed how they developed their questionnaire and only a quarter of studies (28%) mentioned the validity or reliability of the questionnaire. The only characteristic that improved over the years was the proportion of articles reporting missing data (2001-2004: 46.4%; 2005-2008: 61.9%; and 2009-2011: 84.8%; respectively) (P<0.01)., Conclusions: The quality of survey reporting in nephrology journals remains suboptimal. In particular, reporting of the validity and reliability of the questionnaire must be improved. Guidelines to improve survey reporting and increase transparency are clearly needed., (Copyright © 2014 by the American Society of Nephrology.)

Purpose: Clonidine is often used as a sedative in critically ill children, but its effectiveness has not been evaluated in a large, rigorous randomized controlled trial. Our objectives in this pilot trial were to assess the feasibility of a larger trial with respect to (1) effective screening, (2) recruitment, (3) timely drug administration, and (4) protocol adherence., Materials and Methods: This is a randomized, blinded, placebo-controlled pilot trial. Mechanically ventilated children received enteral clonidine 5 μg/kg or placebo every 6 hours; additional sedatives were at the discretion of attending physicians., Results: We enrolled 50 children. The median interquartile range (IQR) age was 2.5 (0.7-5.2) years, and Pediatric Risk of Mortality score on pediatric intensive care unit admission was 12 (8-15). In terms of feasibility outcomes, 90 (87%) of 104 eligible patients were approached for consent, and on average, 1.7 children were enrolled per month. Thirty-five (70%) were enrolled within 1 day of becoming eligible (mean, 1.2 days). Thereafter, 94% of doses were administered by protocol. Clinical outcomes and adverse effects were not significantly different between the groups., Conclusions: This pilot trial demonstrated feasibility of a larger randomized controlled trial. Some important challenges emerged, allowing refinement of the study protocol and enrolment estimates. We recommend that future trials capitalize on the experience gained and use these results to design a larger trial focusing on clinically important outcomes., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: The objective of this study was to identify the self-reported barriers to and facilitators of prescribing low-molecular-weight heparin (LMWH) thromboprophylaxis in the intensive care unit (ICU)., Methods: We conducted an interviewer-administered survey of 4 individuals per ICU (the ICU director, a bedside pharmacist, a thromboprophylaxis research coordinator, and physician site investigator) regarding LMWH thromboprophylaxis for medical-surgical patients in 27 ICUs in Canada and the United States. Items were generated by the research team and adapted from previous surveys, audits, qualitative studies, and quality improvement research. Respondents rated the barriers to LMWH use, facilitators (effectiveness, affordability, and acceptability thereof), and perceptions regarding LMWH use., Results: Respondents had 14.5 (SD, 7.7) years of ICU experience (response rate, 99%). The 5 most common barriers in descending order were as follows: drug acquisition cost, fear of bleeding, lack of resident education, concern about bioaccumulation in renal failure, and habit. The top 5 rated facilitators were preprinted orders, education, daily reminders, audit and feedback, and local quality improvement committee endorsement. Centers using preprinted orders (mean difference [P<.01]) and computerized physician order entry (P<.01) compared with those centers not using those tools reported higher affordability for these 2 facilitators. Compared with physicians and pharmacists, research coordinators considered ICU-specific audit and feedback of thromboprophylaxis rates to be a more effective, acceptable, and affordable facilitator (odds ratio, 6.67; 95% confidence interval, 1.97-22.53; P<.01). Facilitator acceptability ratings were similar within centers but differed across centers (P≤.01)., Conclusions: This multicenter survey found several barriers to use of LMWH including cost, concern about bleeding, and lack of resident knowledge of effectiveness. The diversity of reported facilitators suggests that large scale programs may address generic barriers but also need site-specific interprofessional knowledge translation activities., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Introduction: Evidence from randomized controlled trials (RCTs) is required to guide treatment of critically ill children, but the number of RCTs available is limited and the publications are often difficult to find. The objectives of this review were to systematically identify RCTs in pediatric critical care and describe their methods and reporting., Methods: We searched MEDLINE, EMBASE, LILACS and CENTRAL (from inception to April 16, 2013) and reference lists of included RCTs and relevant systematic reviews. We included published RCTs administering any intervention to children in a pediatric ICU. We excluded trials conducted in neonatal ICUs, those enrolling exclusively preterm infants, and individual patient crossover trials. Pairs of reviewers independently screened studies for eligibility, assessed risk of bias, and abstracted data. Discrepancies were resolved by consensus., Results: We included 248 RCTs: 45 (18%) were multicentered and 14 (6%) were multinational. Trials most frequently enrolled both medical and surgical patients (43%) but postoperative cardiac surgery was the single largest population studied (19%). The most frequently evaluated types of intervention were medications (63%), devices (11%) and nutrition (8%). Laboratory or physiological measurements were the most frequent type of primary outcomes (18%). Half of these trials (50%) reported blinding. Of the 107 (43%) trials that reported an a priori sample size, 34 (32%) were stopped early. The median number of children randomized per trial was 49 and ranged from 6 to 4,947. The frequency of RCT publications increased at a mean rate of 0.7 RCTs per year (P<0.001) from 1 to 20 trials per year., Conclusions: This scoping review identified the available RCTs in pediatric critical care and made them accessible to clinicians and researchers (http://epicc.mcmaster.ca). Most focused on medications and intermediate or surrogate outcomes, were single-centered and were conducted in North America and Western Europe. The results of this review underscore the need for trials with rigorous methodology, appropriate outcome measures, and improved quality of reporting to ensure that high quality evidence exists to support clinical decision-making in this vulnerable population.

Background: Research projects are a key component of pharmacy residents' education. Projects represent both a large investment of effort for each resident (up to 10 weeks over the residency year) and a large body of research (given that there are currently over 150 residency positions in Canada annually). Publication of results is a vital part of the dissemination of information gleaned from these projects., Objectives: To determine the publication rate for research projects performed under the auspices of accredited English-language hospital pharmacy residency programs in Canada and to describe the study characteristics of residency projects performed in Ontario from 1999/2000 to 2008/2009., Methods: Lists of residents and project titles for the period of interest were obtained from residency coordinators. PubMed, CINAHL, the Canadian Journal of Hospital Pharmacy, and Google were searched for evidence of publication of each project identified, as an abstract or presentation at a meeting, a letter to the editor, or a full-text manuscript. The library holdings of the University of Toronto were reviewed to determine study characteristics of the Ontario residency projects., Results: For the objective of this study relating to publication rate, 518 projects were included. The overall publication rate was 32.2% (60 [35.9%] as abstracts and 107 [64.1%] as full-text manuscripts). Publication in pharmacy-specific journals (66 [61.7%] of 107 full-text manuscripts) was more frequent than publication in non-pharmacy-specific journals. The publication rate of projects as full-text manuscripts remained stable over time. Of the 202 Ontario residency projects archived in the University of Toronto's library, most were cohort studies (83 [41.1%]), and the most common topic was efficacy and/or safety of a medication (46 [22.8%])., Conclusions: Most hospital pharmacy residents' projects were unpublished, and the publication rate of projects as full-text manuscripts has not increased over time. Most projects were observational studies. Increasing publication rates and creating a central database or repository of residency projects would increase the dissemination and accessibility of residents' research.

Young infants with bronchiolitis commonly present with apnea. Caffeine is effective in treating apnea of prematurity and has been used to treat apnea associated with bronchiolitis. To evaluate whether caffeine administration to infants presenting with apnea in the setting of bronchiolitis was associated with a decreased rate of endotracheal intubation and mechanical ventilation, compared to infants who did not receive caffeine. Retrospective cohort study. University affiliated tertiary care children's hospital. Twenty-eight infants less than 3 months of age, 13 of whom received caffeine. Fewer infants who received caffeine required endotracheal intubation and invasive mechanical ventilation (OR = 0.30 95% CI 0.07 to 1.4, p = 0.15), but this was not statistically significant. Infants who received caffeine were more likely to be treated with non-invasive ventilation than infants in the control group (OR = 14; 95% CI 2.1 to 98 p = 0.01). Only one patient who was initially managed with non-invasive ventilation was subsequently intubated. There was no difference in the duration of total respiratory support, duration of invasive mechanical ventilation, hospital and pediatric critical care unit stay. All infants survived. This study does not provide adequate evidence to support or refute the routine use of caffeine in bronchiolitis associated apnea.

Objective . To summarize clinical research related to the effect of clonidine on sedation, signs and symptoms of withdrawal, and other adverse events among mechanically ventilated children. Data Sources . We searched MEDLINE, EMBASE, CINAHL, LILACS and the Cochrane Central Register of Controlled Trials, trial registries and conference proceedings. Study Selection . We included all observational and experimental studies that reported the transdermal, intravenous or enteral administration of clonidine to mechanically ventilated, critically ill pediatric patients. Data Extraction. We extracted data on the effect of clonidine on sedation, withdrawal, duration of ventilation and adverse effects and did not attempt to quantitatively combine the results due to the heterogeneous study design and patient populations. Data Synthesis . This review includes 4 case reports, two retrospective cohort studies (total of 58 children), two prospective uncontrolled studies (total of 55 children) and one randomized controlled trial (69 children). In general, efforts to minimize known sources of bias were modest and all studies used non-validated tools for measuring withdrawal. Small observational studies suggest an improvement in withdrawal symptoms and adequacy of sedation with clonidine therapy; however, the small randomized trial found no effect on these or on the duration of ventilation. Results of these small studies have limited generalizability and provide imprecise estimates of treatment effects. Conclusions . Clonidine has been used as a sedative and analgesic agent to prevent and treat withdrawal in critically ill intubated children. Current clinical studies are inadequate to assess its benefits and harms, and do not support current widespread use.

Introduction: Patients with septic shock often receive intravenous vasopressor infusions, with little evidence available to guide their titration. We surveyed Canadian intensivists to document self-reported vasopressor titration strategies for patients with septic shock., Methods: We identified Canadian intensivists caring for adult patients by merging membership lists of 3 Canadian critical care associations. We invited respondents to complete a scenario-based questionnaire to understand triggers for vasopressor use, target blood pressure values, and the influence of chronic comorbidities and acute illnesses on vasopressor prescription., Results: Sixty-three percent of eligible intensivists completed our survey. Most respondents (82.6%) would frequently or always administer vasopressor therapy for isolated hypotension but not for other isolated signs of organ failure (such as elevated serum lactate or low urine output). Respondents defined low blood pressure using mean arterial pressure (83.7%) and aimed for higher values when resuscitating a patient with multiple organ failure. Chronic comorbidities and acute concurrent illnesses had variable effects on stated vasopressor prescription. Norepinephrine (94.8%) was the preferred first-line vasopressor., Conclusions: Self-reported vasopressor use for the treatment of septic shock is relatively uniform among Canadian intensivists; however, practice is variable in patients with chronic comorbidities or acute concurrent illnesses., (Copyright © 2011. Published by Elsevier Inc.)

Purpose: Reliance on third party consent for patients without decision-making capacity presents unique challenges for critical care research. We compared the attitudes and beliefs of Canadian research ethics boards (REBs) and intensive care unit researchers toward the use of various consent models for a low-risk randomized controlled trial., Materials and Methods: Self-administered, scenario-based survey., Results: Sixty-two percent of eligible REBs (n = 83) and 78% of eligible researchers (n = 124) completed the questionnaire. The REBs were less comfortable endorsing alternative consent models when a substitute decision maker was unavailable, including consent provided by (a) the intensivist involved with the trial (2.0% vs 15.3%; P = .014), (b) the intensivist not involved with the trial (10.0% vs 36.7%; P = .001), (c) 2 physicians (the intensivist and another consultant, neither of whom is involved with the trial) (18.0% vs 54.1%; P < .001), and (d) 2 physicians involved neither with the trial nor the patient's care (10.2% vs 52.0%; P < .001). In similar circumstances, REBs were less comfortable approving both deferred (8.0% vs 43.3%; P < .001) and waived (4.1% vs 22.4%; P = .005) consent., Conclusions: In this survey of scenarios involving low-risk critical care research, REBs were significantly more conservative in approving alternative consent models compared with investigators., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: To assess the general public's attitudes toward various consent models and data management strategies for critically ill adults eligible to participate in a low-risk randomized trial., Methods: A self-administered survey was conducted at public locations in Toronto to elucidate the general public's attitudes toward various consent models for participation in a low-risk randomized trial when a substitute decision maker was available, unavailable, or did not exist, as well as to assess attitudes toward strategies for data management in patients enrolled under a substitute decision maker's consent who later decline further participation., Results: We surveyed 221 citizens. Most respondents (64%-74%) wanted to be considered for participation. When a substitute decision maker was available, similar proportions of respondents were comfortable with the substitute decision maker providing consent, deferred consent, and their substitute decision maker being asked if the respondent would "object to participating." If a substitute existed but was unavailable, most participants were comfortable with waived consent. If a substitute did not exist, respondents expressed comfort with 4 consent models: an attending physician model, a 2-physician model (1 involved in care), deferred consent, and waived consent. Compared with any physician, respondents preferred their attending physician to be involved in decisions about their research participation, especially in the absence of a substitute decision maker. Nearly three-fourths of respondents supported data management strategies that enabled use of their primary outcome; moreover, 58% believed that data collected before their decision to decline further participation should be included., Conclusions: Most respondents were interested in participating in a low-risk trial. Respondents endorsed a variety of approaches to obtaining consent in the presence or absence of substitute decision makers and many would be comfortable if their data were used despite a decision to decline further participation.

Objective: Certain methodologic features of animal experiments such as random assignment have been found to reduce the risk of bias. Because animal research sometimes informs clinical practice, explicit acknowledgment of the risk of bias and clinical relevance cultivates realistic expectations on the part of clinicians reading preclinical studies. We assessed literature reviews of therapeutic interventions for sepsis that include animal experiments for explicit appraisals of the risk of bias and clinical relevance., Data Sources: MEDLINE and EMBASE., Study Selection: Systematic reviews or meta-analyses of animal experiments focusing on therapeutic interventions for sepsis., Data Extraction: In teams of two, reviewers independently screened citations and abstracted data. We determined whether the reviews systematically incorporated critical appraisals for the risk of bias and clinical relevance of the underlying studies as well as explicit extrapolations from preclinical research to human patients., Data Synthesis: From 164 citations, we retained 45 reviews. Chance-corrected agreement for inclusion was moderate (κ 0.57). Three (7%) met our criteria for a systematic review and one (2%) systematically appraised the risk of bias and the clinical relevance of the primary animal experiments. Thirty-six (80%) were narrative reviews addressing issues related to diverse topics such as pathophysiology and diagnosis as well as multiple therapies and 40 of 45 (89%) included both clinical and animal studies. Twelve (27%) explicitly assumed that data from preclinical studies could apply to human patients., Conclusions: Although a significant proportion of reviews extrapolated preclinical study results to human patients, most did not systematically appraise the risk of bias or the clinical relevance of preclinical research. Because animal experiments may influence clinical practice, we propose a framework to enhance these features in future reviews of preclinical research.